The overall objective of the proposed studies is to understand how extrathyroidal factors affect the distribution and target tissue uptake of thyroid hormones. The proposal has two major parts. 1. A novel computer based method of kinetic analysis will be employed to analyze single injection tracer disappearance curves in terms of the distribution of recirculation times for exchangeable thyroxine and triiodothyronine. Studies will be carried out in normals and patients with decreased serum iodothyronine binding to determine whether, as postulated, decreased binding diminishes the proportion of total exchangeable thyroid hormones in tissues such as muscle which have slow recirculation times. 2. Studies of the nuclear triiodothyronine receptor will focus on the role of organic phosphate in T3 binding and the effect of binding on nonhistone protein phosphorylation. Evidence of metabolic control of T3 receptor activity will be sought.